FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
PERTZYE® is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
PERTZYE is not substitutable with any other pancrelipase products.
PERTZYE is administered orally or via a gastrostomy tube. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of PERTZYE should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see Limitations on Dosing below).
PERTZYE is a mixture of enzymes including lipases, proteases, and amylases and dosing is based on lipase units. Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1,2,3 PERTZYE should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.
Infants (up to 12 months)
Infants may be given 4,000 lipase units (one capsule) per 120 mL of formula or breast-feeding. Do not mix PERTZYE capsule contents directly into formula or breast milk prior to administration [see Dosage and Administration (2.2)].
Children Older than 12 Months and Younger than 4 Years
Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.
Children 4 Years and Older and Adults
Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.
Usually, half of the prescribed PERTZYE dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day.
Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients because they weigh more but tend to ingest less fat per kilogram of body weight.
Limitations on Dosing
Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines.1,2,3
If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted.
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures, indicative of fibrosing colonopathy, in children with cystic fibrosis less than 12 years of age [see Warnings and Precautions (5.1)]. Patients currently receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
2.2 Administration
PERTZYE should always be taken as prescribed by a healthcare professional.
Infants (up to 12 months)
PERTZYE should be administered to infants immediately prior to each feeding, using a dosage of 4,000 lipase units (one capsule) per 120 mL of formula or per breast-feeding. Contents of the capsule may be mixed with approximately 10 mL of soft acidic food with a pH of 4.5 or less (e.g., applesauce). Contents of the capsule may also be administered directly to the mouth. Administration should be followed by breast milk or formula. Do not mix contents of the capsule directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that the PERTZYE capsule contents (microspheres) are not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa [see Warnings and Precautions (5.2)].
Children and Adults
- Administer PERTZYE during meals or snacks, with sufficient fluid.
- Swallow PERTZYE capsules whole.
- If a dose is missed, take the next dose with the next meal or snack as directed. Do not take two doses at one time.
- Do not crush or chew the capsules or the capsule contents (microspheres).
- For patients who are unable to swallow intact capsules, follow the instructions below for oral administration with soft foods with a pH of 4.5 or less (e.g., applesauce):
- Place a small amount (approximately 10 mL) of applesauce into a clean container.
- Carefully open the capsule(s).
- Sprinkle the entire contents (microspheres) on the applesauce.
- Mix the capsule contents (microspheres) with the applesauce being careful not to crush the microspheres when mixing.
- Consume the entire mixture immediately. Do not chew the capsule contents (microspheres). Do not save the mixture for later use.
- Follow with water or juice to ensure complete ingestion and to ensure nothing is retained in the mouth to avoid mucosal irritation [see Warnings and Precautions (5.2)].
Alternatively, the contents of one or two 4,000 USP lipase unit capsules can be administered with soft foods with a pH of 4.0 or less (e.g., applesauce) via a gastrostomy tube with a diameter of 14 French or larger.
Gastrostomy Tube Administration Instructions (14 French Gastrostomy Tube or Larger)
Only perform gastrostomy tube administration with the contents of the 4,000 USP lipase unit capsule of PERTZYE. The contents of no more than two capsules may be administered at a time.
- Transfer a minimum of 10 mL of applesauce into a small bowl or medicine cup.
- Carefully open one or two Pertzye 4,000 lipase unit capsules.
- Mix the capsule contents (microspheres) thoroughly with the transferred applesauce to create a uniform suspension. Once mixed, administer the suspension immediately. Care should be taken not to crush the microspheres when mixing. Discard the empty capsules.
- Remove the plunger from a 35 mL slip tip syringe. Cover the tip of the syringe with your finger. Transfer the PERTZYE-applesauce mixture into the syringe. Replace the plunger partially back into the syringe.
- Shake or tap the syringe lightly with the syringe tip facing upward so that the PERTZYE-applesauce mixture will move towards the plunger. Carefully push the plunger slowly until the residual air is removed from the syringe tip.
- Once the residual air is removed, connect the syringe directly into the gastrostomy tube feeding port.
- Push the syringe contents into the gastrostomy tube feeding port using steady pressure until empty.
- Draw up approximately 10 mL of water with the slip tip syringe and flush the gastrostomy tube feeding port with the water.
- Discard any unused portion of the PERTZYE-applesauce mixture. Do not save for later use.
- If dose requires more than two capsules, repeat steps 1-9 until prescribed dose is reached.
3 DOSAGE FORMS AND STRENGTHS
Delayed-release capsules are available in the following strengths:
- 4,000 USP units of lipase; 14,375 USP units of protease; 15,125 USP units of amylase. Delayed-release capsules have a clear body printed in green with "4" and a clear cap printed with a green circular stripe and "DCI"
- 8,000 USP units of lipase; 28,750 USP units of protease; 30,250 USP units of amylase. Delayed-release capsules have a clear body printed in blue with "8" and a clear cap printed with a blue circular stripe and "DCI"
- 16,000 USP units of lipase; 57,500 USP units of protease; 60,500 USP units of amylase. Delayed-release capsules have a clear body printed in red with "16" and a clear cap printed with a red circular stripe and "DCI"
- 24,000 USP units of lipase; 86,250 USP units of protease; 90,750 USP units of amylase. Delayed-release capsules have a clear body printed in purple with "24" and a clear cap printed with a purple circular stripe and "DCI"
5 WARNINGS AND PRECAUTIONS
5.1 Fibrosing Colonopathy
Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day [see Dosage and Administration (2.1)].
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
5.2 Potential for Irritation to Oral Mucosa
Care should be taken to ensure that no drug is retained in the mouth. PERTZYE should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity [see Dosage and Administration (2.2)]. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents mixed with a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce, or administered with applesauce via a gastrostomy tube with a diameter of 14 French or larger (only for the 4,000 USP lipase unit capsule strength) [see Dosage and Administration (2.2)]. If administered orally, the PERTZYE-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.
5.3 Potential for Risk of Hyperuricemia
Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels. Consider monitoring serum uric acid levels in patients with hyperuricemia, gout, or renal impairment.
5.4 Potential Viral Exposure from the Product Source
PERTZYE is sourced from pancreatic tissue from swine used for food consumption. Although the risk that PERTZYE will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.
5.5 Allergic Reactions
Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued PERTZYE treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.
6 ADVERSE REACTIONS
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions [see Warnings and Precautions (5.1, 5.3, 5.5)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The short-term safety of PERTZYE was assessed in a randomized, double-blind, placebo- controlled, crossover study of 24 patients, ages 8 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. In this study, patients were randomized to receive PERTZYE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) or matching placebo for 6 to 8 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 8 days. The length of exposure to PERTZYE during this study was 20-28 days, including the treatment period of 6 to 8 days, and the open label titration and transition periods of 7 to 10 days.
The most common adverse reactions (≥10%) were diarrhea, dyspepsia, and cough. Table 1 enumerates adverse reactions that occurred in at least 2 patients (greater than or equal to 10%) treated with PERTZYE at a higher rate than with placebo.
| Adverse Reaction | PERTZYE n=21 n (%) | PLACEBO n=24 n (%) |
|---|---|---|
| Diarrhea | 2 (10%) | 1 (4%) |
| Dyspepsia | 2 (10%) | 1 (4%) |
| Cough | 2 (10%) | 1 (4%) |
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of PERTZYE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
This formulation of PERTZYE has been marketed since 2004 under the trademark PANCRECARB®. Two product complaints relating to an adverse drug reaction were reported. A mild allergic reaction (itching and red, blotchy rash on face) was reported by a patient with a known history of allergy to another pancrelipase product, and a dull headache was reported by another patient taking concomitant ursodeoxycholic acid. Both events resolved without sequelae after discontinuation of treatment.
Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events include fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders, including pruritus, urticaria and rash.
7 DRUG INTERACTIONS
No drug interactions have been identified. No formal interaction studies have been conducted.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Published data from case reports with pancrelipase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Pancrelipase is minimally absorbed systematically; therefore, maternal use is not expected to result in fetal exposure to the drug. Animal reproduction studies have not been conducted with pancrelipase.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
8.2 Lactation
Risk Summary
There are no data on the presence of pancrelipase in either human or animal milk, the effects on the breastfed infant or the effects on milk production. Pancrelipase is minimally absorbed systemically following oral administration, therefore maternal use is not expected to result in clinically relevant exposure of breastfed infants to the drug. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PERTZYE and any potential adverse effects on the breastfed infant from PERTZYE or from the underlying maternal condition.
8.4 Pediatric Use
The short-term safety and efficacy of PERTZYE were assessed in a randomized, double- blind, placebo-controlled, crossover study of 24 patients with exocrine pancreatic insufficiency due to cystic fibrosis, including 10 patients between 8 and 17 years of age. The safety and efficacy in 8 to 17 year old patients in this study were similar to adult patients [see Adverse Reactions (6.1) and Clinical Studies (14)].
The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis have been described in the medical literature and through clinical experience.
Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences [see Dosage and Administration (2.1)]. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age [see Warnings and Precautions (5.1)].
10 OVERDOSAGE
In a clinical study, a 10 year-old patient was administered lipase doses over the maximum lipase dose of 2500 lipase units/kg/meal (Dose Stabilization 2799 lipase units/kg/meal; Wash-out/Re-Stabilization 2783 lipase units/kg/meal; and PERTZYE 2720 lipase units/kg/meal). Despite the administration of this slightly (10%) higher than recommended dose, no gastrointestinal AEs were reported for this subject.
Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment [see Warnings and Precautions (5.3)].
11 DESCRIPTION
Pancrelipase is a pancreatic enzyme product consisting of a mixture of enzymes including lipases, proteases, and amylases, and is an extract derived from porcine pancreatic glands.
PERTZYE (pancrelipase) delayed-release capsule for oral administration contains bicarbonate-buffered enteric-coated microspheres ranging in size from 0.8 to 1.4 mm in diameter for 4,000 USP units of lipase and 0.8 to 2.2 mm in diameter for 8,000, 16,000, and 24,000 USP units of lipase.
4,000 USP units of lipase; 14,375 USP units of protease; 15,125 USP units of amylase. Delayed-Release Capsules have a clear body printed in green with "4" and a clear cap printed with a green circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #1, D&C Yellow #10, black iron oxide, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, shellac and ammonium hydroxide.
8,000 USP units of lipase; 28,750 USP units of protease; 30,250 USP units of amylase. Delayed-Release Capsules have a clear body printed in blue with "8" and a clear cap printed with a blue circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #1, ethanol, methanol, n-butyl alcohol, propylene glycol, shellac and ammonium hydroxide.
16,000 USP units of lipase; 57,500 USP units of protease; 60,500 USP units of amylase. Delayed-Release Capsules have a clear body printed in red with "16" and a clear cap printed with a red circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Red #40, povidone, titanium dioxide, dehydrated alcohol, sodium hydroxide, butyl alcohol, propylene glycol, isopropyl alcohol, and shellac.
24,000 USP units of lipase; 86,250 USP units of protease; 90,750 USP units of amylase. Delayed-Release Capsules have a clear body printed in purple with "24" and a clear cap printed with a purple circular stripe and "DCI". The imprinting ink on the capsule contains FD&C Blue #2, D&C Red #7, titanium dioxide, strong ammonia solution, propylene glycol, butyl alcohol, isopropyl alcohol, dehydrated alcohol, and shellac.
Inactive ingredients in PERTZYE include cellulose acetate phthalate, diethyl phthalate, polyvinylpyrrolidone, sodium bicarbonate, sodium carbonate, sodium starch glycolate, talc, and ursodiol, and are contained in hard gelatin capsules.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The pancreatic enzymes in PERTZYE catalyze the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltotriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.
12.3 Pharmacokinetics
The pancreatic enzymes in PERTZYE are enteric-coated to minimize destruction or inactivation in gastric acid. PERTZYE is expected to release most of the enzymes in vivo at pH greater than 5.5. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.
14 CLINICAL STUDIES
The short-term safety and efficacy of PERTZYE were evaluated in a randomized, double- blind, placebo-controlled, crossover study conducted in 24 patients ages 8 to 43 years (mean age = 20 years) with exocrine pancreatic insufficiency due to cystic fibrosis.6 The efficacy analysis population included 21 patients who completed both double-blind treatment periods. Patients were randomized to receive PERTZYE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) or matching placebo for 6 to 8 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 8 days.
The primary efficacy endpoint was the mean difference in coefficient of fat absorption (CFA) between PERTZYE and placebo treatment. The CFA was determined by a 72-hour stool collection during both treatments, when both fat ingestion and excretion were measured.
Mean CFA was 83% with PERTZYE treatment compared to 46% with placebo treatment. The mean difference in CFA was 36 percentage points in favor of PERTZYE treatment with 95% CI: (28, 45) and p<0.001.
The coefficient of nitrogen absorption (CNA) was determined by a 72-hour stool collection during both treatments, when nitrogen excretion was measured and nitrogen ingestion from a controlled diet was estimated (based on the assumption that proteins contain 16% nitrogen). Each patient's CNA during placebo treatment was used as their no-treatment CNA value. Mean CNA was 79% with PERTZYE treatment compared to 47% with placebo treatment. The mean difference in CNA was 32 percentage points in favor of PERTZYE treatment and this was a statistically significant change.
There were no differences between children and adults in the severity of pancreatic insufficiency (placebo response) or in the magnitude of the response to PERTZYE.
15 REFERENCES
- Borowitz DS, Grand RJ, Durie PR, et al. Use of pancreatic enzyme supplements for patients with cystic fibrosis in the context of fibrosing colonopathy. Journal of Pediatrics. 1995; 127: 681-684.
- Borowitz DS, Baker RD, Stallings V. Consensus report on nutrition for pediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology Nutrition. 2002 Sep; 35: 246-259.
- Stallings VA, Start LJ, Robinson KA, et al. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. Journal of the American Dietetic Association. 2008; 108: 832-839.
- Smyth RL, Ashby D, O'Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-control study. Lancet. 1995; 346: 1247-1251.
- FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. New England Journal of Medicine. 1997; 336: 1283-1289.
- Konstan MW, et al. A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Cross-Over Study to Evaluate the Effectiveness and Safety of a Novel Pancrelipase (PANCRECARB® MS-16) in Reducing Steatorrhea in Children and Adults with Cystic Fibrosis. 2008 North American Cystic Fibrosis Conference. Abstract #618.
16 HOW SUPPLIED/STORAGE AND HANDLING
PERTZYE (pancrelipase) Delayed-Release Capsules
4,000 USP units of lipase; 14,375 USP units of protease; 15,125 USP units of amylase. Each PERTZYE delayed-release capsule has a clear body printed in green with "4" and a clear cap printed with a green circular stripe and "DCI". Delayed-release capsules are supplied in bottles of 100 (NDC 59767-004-01).
PERTZYE (pancrelipase) Delayed-Release Capsules
8,000 USP units of lipase; 28,750 USP units of protease; 30,250 USP units of amylase. Each PERTZYE delayed-release capsule has a clear body printed in blue with "8" and a clear cap printed with a blue circular stripe and "DCI". Delayed-release capsules are supplied in bottles of 100 (NDC 59767-008-01) or 250 (NDC 59767-008-02).
PERTZYE (pancrelipase) Delayed-Release Capsules
16,000 USP units of lipase; 57,500 USP units of protease; 60,500 USP units of amylase. Each PERTZYE delayed-release capsule has a clear body printed in red with "16" and a clear cap printed with a red circular stripe and "DCI". Delayed-release capsules are supplied in bottles of 100 (NDC 59767-016-01) or 250 (NDC 59767-016-02).
PERTZYE (pancrelipase) Delayed-Release Capsules
24,000 USP units of lipase; 86,250 USP units of protease; 90,750 USP units of amylase. Each PERTZYE delayed-release capsule has a clear body printed in purple with "24" and a clear cap printed with a purple circular stripe and "DCI". Delayed-release capsules are supplied in bottles of 80 (NDC 59767-024-01) or 200 (NDC 59767-024-02).
Storage and Handling
Store at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 40°C (59°F to 104°F) for up to 30 days. PERTZYE hard gelatin capsules should be stored in a dry place in the original container or equivalent air tight container. After opening, keep the container tightly closed between uses to protect from moisture.
PERTZYE is dispensed in bottles containing a desiccant. The desiccant packet should not be eaten or thrown away. The desiccant packet will protect the product from moisture.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Dosing and Administration
Instruct patients and caregivers:
- Administer PERTZYE during meals or snacks, with sufficient fluid.
- Swallow PERTZYE capsules whole.
- Do not crush or chew the capsules or the capsule contents [see Warnings and Precautions (5.2)].
- For patients who are unable to swallow intact capsules, follow the instructions in the Medication Guide for:
- oral administration with soft foods with a pH of 4.5 or less (e.g., applesauce); or
- administration via a gastrostomy tube with a diameter of 14 French or larger with soft foods with a pH of 4.0 or less (e.g., applesauce). Only perform gastrostomy tube administration with the contents of the 4,000 USP lipase unit capsule of PERTZYE. The contents of no more than two capsules may be administered at a time [see Dosage and Administration (2.2)].
- If a dose is missed the next dose should be taken with the next meal or snack as directed. Do not take two doses at one time [see Dosage and Administration (2)].
- After opening the bottle containing PERTZYE, keep it tightly closed between uses. Do not eat or throw away the desiccant packet.
Fibrosing Colonopathy
High doses of pancreatic enzyme products have been associated with colonic strictures in children below the age of 12 years. Advise patients and caregivers that if signs and symptoms of stricture formation occur (e.g., stomach area (abdominal) pain, bloating, trouble passing stool (constipation), nausea, vomiting, diarrhea) to immediately contact their healthcare provider [see Dosage and Administration (2), Warnings and Precautions (5.1)].
Allergic Reactions
Allergic reactions, including anaphylaxis, asthma, hives and pruritus may occur. Advise patients and caregivers to immediately contact their healthcare provider if symptoms occur [see Warnings and Precautions (5.5)].
Manufactured by:
Digestive Care, Inc.
1120 Win Drive
Bethlehem, PA 18017
U.S. License No. 2184
Product of USA
PERTZYE® is a registered trademark of Digestive Care, Inc.
U.S. Patent Numbers: 5,260,074; 5,302,400; 5,324,514; 5,460,812; 5,578,304; 5,750,104
| This Medication Guide has been approved by the U.S. Food and Drug Administration. | Revised: 9/2022 | ||
| MEDICATION GUIDE PERTZYE (pert-zye) (pancrelipase) delayed-release capsules |
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| What is the most important information I should know about PERTZYE?
PERTZYE may increase the risk of having a rare bowel disorder called fibrosing colonopathy, especially if taken at a high dose in children with cystic fibrosis who are less than 12 years of age. This condition is serious and may require surgery. The risk of having fibrosing colonopathy may be reduced by following the dosing instructions that your doctor gives you. Call your doctor right away if you have any unusual or severe: |
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| Take PERTZYE exactly as prescribed by your doctor. Do not take more PERTZYE than your doctor tells you to. | |||
What is PERTZYE?
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Before taking PERTZYE, tell your doctor about all of your medical conditions, including if you:
Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. |
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How should I take PERTZYE?
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What are the possible side effects of PERTZYE?
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| Call your doctor right away if you have any of these symptoms. The most common side effects of PERTZYE include: |
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| Other possible side effects:
PERTZYE and other pancreatic enzyme products are made from the pancreas of pigs, the same pigs people eat as pork. These pigs may carry viruses. Although it has never been reported, it may be possible for a person to get a viral infection from taking pancreatic enzyme products that come from pigs. These are not all of the possible side effects of PERTZYE. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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How should I store PERTZYE?
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| General information about the safe and effective use of PERTZYE.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use PERTZYE for a condition for which it was not prescribed. Do not give PERTZYE to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about PERTZYE that is written for health professionals. |
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| What are the ingredients in PERTZYE?
Active ingredients: lipase, protease, and amylase. Inactive ingredients: sodium bicarbonate, sodium carbonate, cellulose acetate phthalate, sodium starch glycolate, diethyl phthalate, ursodiol, polyvinylpyrrolidone, and talc. The hard gelatin capsule shells contain: gelatin and water. The green imprinting ink on the 4,000 units of lipase; 14,375 units of protease; 15,125 units of amylase capsules contain: FD&C Blue #1, D&C Yellow #10, black iron oxide, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, shellac and ammonium hydroxide. The blue imprinting ink on the 8,000 units of lipase; 28,750 units of protease; 30,250 units of amylase capsules contain: FD&C Blue #1, ethanol, methanol, n-butyl alcohol, propylene glycol, shellac and ammonium hydroxide. The red imprinting ink on the 16,000 units of lipase; 57,500 units of protease; 60,500 units of amylase capsules contain: FD&C Red #40, povidone, titanium dioxide, dehydrated alcohol, sodium hydroxide, butyl alcohol, propylene glycol, isopropyl alcohol, and shellac. The purple imprinting ink on the 24,000 units of lipase; 86,250 units of protease; 90,750 units of amylase capsules contain: FD&C Blue #2, D&C Red #7, titanium dioxide, strong ammonia solution, propylene glycol, butyl alcohol, isopropyl alcohol, dehydrated alcohol, and shellac. For more information, go to www.Pertzye.com or call 1-877-882-5950. |
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| Manufactured by:
Digestive Care, Inc. 1120 Win Drive Bethlehem, PA 18017 U.S. License No. 2184 Product of USA |
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INSTRUCTIONS FOR USE
PERTZYE (pert-zye)
(pancrelipase)
delayed-release capsules
This "Instructions for Use" contains information on how to give PERTZYE by mouth and through a gastrostomy tube.
Important Information You Need to Know Before Taking PERTZYE:
- Always take PERTZYE with a meal or snack and plenty of fluid.
- PERTZYE capsules should be swallowed whole. Do not crush or chew the PERTZYE capsules or their contents, and do not hold the capsule or capsule contents in your mouth.
- Throw away the PERTZYE capsule contents-food mixture that is not used. Do not save this mixture for later use.
Giving PERTZYE to infants (up to 12 months of age) by mouth:
- Give the contents of 1 PERTZYE capsule right before each feeding of formula or breast milk.
- Do not mix PERTZYE capsule contents directly into formula or breast milk.
-
PERTZYE capsule contents may be given directly into your infant's mouth or mixed with food.
-
Giving PERTZYE capsule contents directly into your infant's mouth:
- 1.
- Carefully open the PERTZYE capsule by grasping and slightly squeezing both ends of the capsule and then twisting and pulling the capsule apart. Empty the capsule contents into your infant's mouth.
- 2.
- Give your infant 4 ounces (120 mL) of formula or breastfeed right away.
- 3.
- Look in your infant's mouth to make sure that all of the medicine is swallowed and there is no PERTZYE capsule contents left in your infant's mouth.
- 4.
- Throw away the empty PERTZYE capsule.
-
Giving PERTZYE capsule contents mixed in food:
- 5.
- Place about 2 teaspoons of applesauce, the kind found in baby food jars that you buy at the store, or other food recommended by your doctor, into a clean container.
- 6.
- Carefully open the PERTZYE capsule by grasping and slightly squeezing both ends of the capsule and then twisting and pulling the capsule apart. Pour the capsule contents onto the food in the clean container. Throw away the empty PERTZYE capsule.
- 7.
- Carefully mix the capsule contents evenly through the food. Be careful not to crush the PERTZYE capsule contents when mixing.
- 8.
- Give the PERTZYE capsule contents-food mixture to your infant right away.
- 9.
- Give your infant 4 ounces (120 mL) of formula or breastfeed your infant right away.
- 10.
- Look in your infant's mouth to make sure that all of the medicine is swallowed and there is no PERTZYE capsule contents-food mixture left in your infant's mouth.
-
Giving PERTZYE capsule contents directly into your infant's mouth:
Giving PERTZYE to children and adults by mouth:
- Swallow PERTZYE capsules whole and take them with enough liquid to swallow them right away.
- If you have trouble swallowing capsules, follow these instructions for taking PERTZYE with food:
- 11.
- Place about 2 teaspoons of applesauce, or other food recommended by your doctor, into a clean container.
- 12.
- Carefully open the capsules that you will need for the prescribed dose by grasping and slightly squeezing both ends of the capsule and then twisting and pulling the capsule apart. Pour the capsule contents onto the food in the clean container. Throw away the empty PERTZYE capsules.
- 13.
- Carefully mix the capsule contents evenly through the food. Be careful not to crush the PERTZYE capsule contents when mixing.
- 14.
- Swallow all of the PERTZYE capsule contents-food mixture right away.
- 15.
- Drink plenty of water or juice to make sure that all of the medicine is swallowed and there is no PERTZYE capsule contents-food mixture left in the mouth.
Giving PERTZYE through a gastrostomy tube:
- PERTZYE 4,000 lipase units capsule contents may be given through a gastrostomy tube that is size 14 French or larger. Do not give PERTZYE through a gastrostomy tube smaller than size 14 French.
- Do not give more than the contents of 2 PERTZYE 4,000 lipase units capsules through a gastrostomy tube at a time.
- Give the PERTZYE capsule contents-food mixture right away after it is prepared.
- 16.
- Place at least 2 teaspoons of applesauce, or other food recommended by your doctor, into a clean container.
- 17.
- Carefully open 1 or 2 of the PERTZYE capsules, depending on your prescribed dose, by grasping and slightly squeezing both ends of the capsule and then twisting and pulling the capsule apart. Pour the capsule contents onto the food in the clean container. Throw away the empty PERTZYE capsules (See Figure A).
Figure A - 18.
- Carefully mix the capsule contents evenly through the food. Be careful not to crush the PERTZYE capsule contents when mixing.
- 19.
- Remove the plunger from a 35 mL slip tip syringe. Cover the tip of the syringe with your finger.
- 20.
- Carefully spoon the PERTZYE capsule contents-food mixture into the slip tip syringe (See Figure B).
Figure B - 21.
- Replace the plunger partially back into the slip tip syringe.
- 22.
- Turn the slip tip syringe so the syringe tip is facing upward. Remove your finger from the tip of the slip tip syringe.
- 23.
- Gently shake or tap the slip tip syringe so that the PERTZYE capsule contents-food mixture moves down towards the plunger.
- 24.
- Carefully push up slowly on the plunger until the PERTZYE capsule contents-food mixture fills the syringe tip (See Figure C).
Figure C - 25.
- Connect the slip tip syringe directly into the gastrostomy tube feeding port.
- 26.
- Press on the plunger of the slip tip syringe using steady pressure to push all of the PERTZYE capsule contents-food mixture into the gastrostomy tube feeding port over 10 seconds to 12 seconds (See Figure D).
Figure D - 27.
- Flush the gastrostomy tube feeding port with about 10 mL of water.
- 28.
- If your prescribed dose is more than 2 capsules of PERTZYE, repeat steps 1 through 12, using only 1 or 2 PERTZYE capsules at a time, until the prescribed dose is given.
Storing PERTZYE:
- Store PERTZYE at room temperature between 68ºF to 77ºF (20°C to 25°C).
- Keep PERTZYE in a dry place and in the original container or equivalent air tight container.
- After opening the bottle, keep it tightly closed between uses to keep your medicine dry (protect it from moisture).
- The PERTZYE bottle contains a desiccant packet to help keep your medicine dry. Do not eat or throw away the desiccant packet in your medicine bottle.
Keep PERTZYE and all medicines out of the reach of children.
Manufactured by:
Digestive Care, Inc.
1120 Win Drive
Bethlehem, PA 18017
U.S. License No. 2184
Product of USA
© 2022 Digestive Care, Inc.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: September 2022
PRINCIPAL DISPLAY PANEL - 100 Capsule Bottle Label - 59767-008
100 Capsules
NDC 59767-008-01
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
8,000 USP Units
Protease
28,750 USP Units
Amylase
30,250 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PROFESSIONAL SAMPLE – NOT FOR RESALE
Please read accompanying Medication Guide
PRINCIPAL DISPLAY PANEL - 250 Capsule Bottle Label - 59767-008
250 Capsules
NDC 59767-008-02
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
8,000 USP Units
Protease
28,750 USP Units
Amylase
30,250 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PRINCIPAL DISPLAY PANEL - 100 Capsule Bottle Label - 59767-004
100 Capsules
NDC 59767-004-01
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
4,000 USP Units
Protease
14,375 USP Units
Amylase
15,125 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PRINCIPAL DISPLAY PANEL - 100 Capsule Bottle Label - 59767-016
100 Capsules
NDC 59767-016-01
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
16,000 USP Units
Protease
57,500 USP Units
Amylase
60,500 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PRINCIPAL DISPLAY PANEL - 250 Capsule Bottle Label - 59767-016
250 Capsules
NDC 59767-016-02
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
16,000 USP Units
Protease
57,500 USP Units
Amylase
60,500 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PRINCIPAL DISPLAY PANEL - 80 Capsule Bottle Label - 59767-024
80 Capsules
NDC 59767-024-01
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
24,000 USP Units
Protease
86,250 USP Units
Amylase
90,750 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
PRINCIPAL DISPLAY PANEL - 200 Capsule Bottle Label - 59767-024
200 Capsules
NDC 59767-024-02
pancrelipase
PERTZYE®
Rx Only
Delayed-Release Capsules
DOSE BY
LIPASE
UNITS
Lipase
24,000 USP Units
Protease
86,250 USP Units
Amylase
90,750 USP Units
Each delayed-release capsule contains pancrelipase
in bicarbonate-buffered enteric-coated microspheres.
This product is of porcine origin. No preservative.
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
